Self-amplification of nigral degeneration in Parkinson's disease: a hypothesis.
This review analyzes current evidence regarding possible mechanisms of nigral damage in idiopathic Parkinson's disease (iPD). In normal brain, a specific interplay among the blood-brain barrier (BBB), substantia nigra (SN), and locus coeruleus (LC) creates the condition for a self-accelerating damage to the SN. Three vicious circles involving SN-BBB, LC-SN-BBB, and histamine-BBB-SN interactions are described. In iPD, a self-accelerating loss of nigral cells can be triggered by brain hypoperfusion and by an increased blood histamine level. iPD-associated factors such as decreased CSF levels of substance P, somatostatin, and glutamate can aggravate the vicious-circle-induced damage to the SN.
Ionov
Ilya D
ID
Center on Problems in Physicochemical Pharmacology, Russian Academy of Sciences, Moscow, Russia. canyon1@rol.ru
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology*; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008125:Locus Coeruleus / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*; D009479:Neuropeptides / Q000378:metabolism; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013378:Substantia Nigra / Q000098:blood supply / Q000378:metabolism / Q000503:physiopathology*
D009479:Neuropeptides; D018698:Glutamic Acid; D006632:Histamine